Objective The aim was to investigate changes in retinal and choroidal thickness (CT) maps in patients with retinitis pigmentosa (RP) in comparison to controls using enhanced depth imaging optical coherence tomography (OCT).Participants and methods A cross-sectional study was done on a consecutive sample of 32 eyes of 22 patients with RP. Control group included 30 eyes of 15 age-matched healthy participants. Full ophthalmological examination was done for every participant. Enhanced depth imaging OCT was performed measuring retinal and CT at the nine early treatment diabetic retinopathy study (ETDRS) subfields.Results The mean central CT was statistically significantly thinner (269.73±48.48 µm) in the patients’ group compared with 291.90±29.33 µm in the control group (P=0.023). On comparing the four choroidal quadrants between the two groups, patients with RP had significantly thinner choroid only in the nasal quadrant (P<0.001). The mean central macular thickness was statistically significantly thinner (226.45±61.35 µm) in the RP group than in controls (247.80±33.74 µm; P=0.009). The four macular quadrants were also significantly thinner in the RP group (P<0.001). Significant positive correlation was found between central macular thickness and central CT (r=0.511, P=0.003) and also at the upper and nasal quadrants (P=0.011 and <0.000,‏ ‏respectively).Conclusion Our study demonstrated that CT is thinned significantly in patients with RP in the central 1 mm and in the nasal quadrant. Evaluation of choroidal vasculature in future studies using OCT angiography may provide further insight into the involvement of choroid in the pathogenesis of RP.

Retinitis pigmentosa (RP) is one of the hereditary degenerative retinal disorders [1]. RP is considered a major cause of blindness, with a prevalence around one in every 3500 births [2].

Clinically, RP is identified by bone spicule pigments, attenuated retinal vessels and a pale, waxy optic disc with photoreceptors degeneration leading to a gradual severe visual loss [3]. Furthermore, night blindness, visual field contraction, and electroretinographic changes are characteristic features of the disease [4].

The pathogenesis of RP has been widely studied, and degeneration of photoreceptors associated with RP is believed to be primarily genetically programmed [5].

However, there has been accumulating evidence suggesting that an additional mechanism associated with RP is the deterioration of retinal oxygenation [6],[7]. This is represented by marked attenuation of the retinal vessels as well as atrophy of the choriocapillaris [5]. Hence, evaluation of the choroid is crucial to understand the pathogenesis of RP.

With the advent of enhanced depth imaging technology (EDI-OCT), changes in choroidal thickness (CT) have been assessed in various retinal diseases. Thus, aiding in comprehending the pathophysiology of these diseases [8],[9].

Recently, few studies have investigated CT in patients with RP with variable results [4],[10],[11].

The aim of this study was to demonstrate the variations in macular retinal and CT maps in patients with RP in comparison with healthy controls using EDI-OCT and to correlate the retinal and CT in various macular zones.

Participants and methods

This cross-sectional clinical study was conducted between December 2017 and April 2018. It included 32 eyes of 22 patients with RP , and their age ranged from 23 to 73 years. Control group included‏ ‏30 eyes of 15 age-matched and sex-matched healthy participants. ‏

The study was conducted in accordance with the ethical standards stated in our institution, with informed consent obtained from every patient.

A consecutive sample of 22 patients diagnosed with RP was recruited. The diagnosis of RP was made based on the clinical history of night blindness, impairment in peripheral visual fields, the presence of characteristic fundus appearance, and the results of full-field electroretinograms with reduction in rod and cone amplitudes.

We excluded patients with diabetes mellitus, eyes with any other ocular pathology (conditions such as cataract, previous ocular trauma, glaucoma, and uveitis), and also eyes with refractive error more than ±3 D. In addition, all cases of macular edema were excluded.

An OCT scan was performed, using spectral domain OCT (retinascan RS-3000 advance; NIDEK), on every patient from 8 a.m. to 12 p.m. Spectral domain OCT scans consisted of 1024 A-scans with high definition, with a 4-µm resolution. We captured a macula map and a macula radial scans (using choroidal mode of the device).

The nine standard retinal subfields in macula map are the central, inner (superior, inferior, nasal, and temporal), and outer (superior, inferior, nasal, and temporal), bounded by 1, 3, and 6-mm diameter circle, respectively. The average of the inner and outer subfield was calculated for each quadrant, and this average was used for statistical analysis.

The sclerachoroidal interface was drawn manually in the 12 radial line scans. CT was measured between the hyper-reflective outer border of the retinal pigment epithelium (RPE) and the line of sclerochoroidal interface, and CT map was automatically generated using the embedded software (NAVIS-EX Image Filing software, RS-3000 advance OCT, NIDEK, Gamagori, Japan). The map included central choroidal thickness (CCT) in the innermost 1-mm circle and other eight subfields as in the macula map ([Figure 1]).

Figure 1 Central macular thickness in the control and retinitis pigmentosa groups.

All data analyses were performed using the statistical package for the social sciences version 23.0 (SPSS v. 23.0; SPSS Inc., Chicago, Illinois, USA). Quantitative data were presented as mean±SD. Qualitative data were compared using χ2-test. Multiple group means of parametric data sets were compared using independent sample t-test. Bivariate Pearson’s correlation and regression analyses were performed. P values were considered significant if less than 0.05.

Results

Our study included 32 eyes of patients with 22 RP, comprising 12 males and 10 females, with mean age of 46.3±16.75 years. Control group included 30 eyes of 15 healthy participants, comprising ‏nine males and six females, with mean age of 46.63‏±15.85 years ([Table 1]).

The mean central macular thickness (CMT) was significantly thinner (226.45±61.35 µm) in the RP group than in the control group (247.80±33.74 µm; P=0.009). The four macular quadrants were significantly thinner in RP than in controls (P<0.001; [Table 2], [Figure 2]).

Table 2 Comparison between retinitis pigmentosa group and control group regarding macular and choroidal thickness in the central 1 mm and in the four quadrants (in microns)

The mean CCT in the central 1 mm was statistically significantly thinner (269.73±48.48 µm) in RP compared with 291.90±29.33 µm in control group (P=0.023). On comparing the four choroidal quadrants between the two groups, patients with RP had significantly thinner choroid only in the nasal quadrant (P<0.001; [Table 2], [Figure 3]).

Correlation analysis between macular and CTs revealed a significant positive correlation between CMT and CCT (r=0.511, P=0.003). Statistically significant positive correlation was also seen at upper and nasal quadrants (P=0.011 and <0.000, respectively). However, no significant correlation was found at the lower and temporal quadrants ([Table 3]).

Table 3 Correlation analysis between retinitis pigmentosa group and control group regarding macular and choroidal thickness in the central 1 mm and in the four quadrants

RP is an inherited retinal dystrophy associated with mutations in more than 45 responsible genes [12]. It involves the progressive loss of rods and consequently cones. The characteristic symptoms include night blindness, followed by peripheral visual field loss and eventually loss of central vision [13].

Although inheritance is the confirmed mode of RP transmission; however, the disorder frequently shows features of inflammatory disturbances. Other recent studies have investigated immune changes in patients with RP [14]. Furthermore, a possible role of blood flow reduction in causing retinal atrophy has been postulated [15].

Previous studies have reported increased endothelin level in patients with RP which has a potential role in choroidal as well as retinal blood flow reduction. Relative choroidal ischemia was more in eyes with a more severe visual loss. Compromised choroidal circulation leads to choriocapillaris atrophy and ultimately rods and cones degeneration [4],[16],[17].

Thus, CT assessment, as a clue to changes in choroidal vasculature or damage to choriocapillaris, may aid in a better understanding of the pathophysiology of RP. It may also be useful for planning future therapies, such as suprachoroidal prosthesis, to calculate the distance between the implant and the ganglion cell layer [18].

The aim of this study was to demonstrate the variations in macular retinal and CT map in patients with RP in comparison with healthy controls and to correlate the retinal and CT in various macular zones, in an attempt to understand the actual pathophysiological changes in RP, which may help in planning and follow-up of various proposed treatment modalities.

To the best of our knowledge, this is the first study to report CT map variations in all macular zones in RP, as all previous studies used single-point subfoveal choroidal thickness (SFCT), which is less accurate in determining the actual difference in CT, and much more liable to measurement error.

Our results showed that the mean CCT in the central 1 mm was statistically significantly thinner (269.7±48.5 µm) in the patient’s group compared with 291.9±29 µm in the control group (P=0.023); in addition, CMT was statistically significantly thinner in the RP group (P=0.009).

Several previous hemodynamic studies showed a reduction in both choroidal and retinal blood flow in RP, by using Doppler imaging [19],[20],[21]. These studies support our findings and suggest that choroidal thinning occurs secondary to decreased circulation.

Previous researches that examined CT in RP reported variable results. In agreement with our results, some studies found significantly lower CT in patients with RP in comparison with controls [4],[10],[22],[23]. Furthermore, an earlier study has reported that mean CMT was significantly thinner in RP [10].

In contrary to our results, Tan et al. [24] demonstrated that patients with RP had a significantly thicker subfoveal CT when compared with normal. They postulate that this may be attributed to fibrosis in the choroid stroma, which thus thickens relative to the choroidal vasculature, and consequently, total CT increases. However, this hypothesis is not validated by any histopathological study [24].

In 2016, Chhablani et al. [11] reported that SFCT did not differ significantly in patients with RP; nevertheless, they only measured single-point SFCT, whereas we measured central 1-mm CT, which is assumed to be more reproducible and less liable to interobserver variability as we already mentioned.

In our study, patients with RP had significantly thinner choroid only in the nasal quadrant (P<0.001), but not in other quadrants. In accordance, Adhi et al. [23], in 2013, demonstrated increased thinning of the nasal choroidal quadrant in patients with RP. This disagrees with the earlier report of Dhoot and his coworkers who reported significantly thinner CT in RP than controls at each of their measurement locations; however, in their study, CT measurements were thinner in the nasal quadrant more than the temporal one in both control and RP groups [10].

As CT may be considered as a rough estimate of alterations in choroidal blood flow or choriocapillaris damage, so our results suggest that choroidal vasculature, as well as retinal layers, are affected in RP. Nevertheless, as only nasal choroidal quadrant is thinned whereas all retinal quadrants were affected, this may suggest that choroidal thinning is not the initiating factor for photoreceptor degeneration.

In our study, we found significant positive correlation between CMT and CCT (r=0.511, P=0.003). Significant positive correlation was also demonstrated at upper and nasal quadrants (P=0.011 and <0.000, respectively). Some earlier reports agreed with our results [23], whereas others disagreed and found no correlation [10]. These results may suggest that degeneration of retina and choroid takes place concurrently in RP.

In conclusion, our study demonstrated that CT is thinned significantly in patients with RP in the central 1 mm and in the nasal quadrant. Future studies using new techniques like OCT angiography may promote our understanding of choroid vasculature changes in RP.

The limitations of this study include that in most of our patients, RP was advanced and photoreceptor layers were not clearly delineated in OCT; hence, we could only measure the total retinal thickness rather than photoreceptor layer thickness. Further studies on patients with early RP are therefore warranted. Limitations also include the cross-sectional nature of the study. A longitudinal study of CT in patients with RP and its correlation with retinal layers’ thickness will better highlight the alteration of the choroid along the course of the disease.